GST genotypes modify the association between paracetamol use in early life and lung function at 18 years

Abstract

Background: While the impact of paracetamol use in early life on asthma risk is still debated, its potential interaction with antioxidative Glutathione S-Transferase (GST) genes, and possible impact on lung function, have not been widely investigated. Aims and objectives: To investigate associations between early life paracetamol use and adolescent asthma and lung function and to assess if these associations are modified by GST gene polymorphisms. Methods: The Melbourne Atopy Cohort Study included 620 children followed from birth to 18 years, with paracetamol use and indications documented 18 times up to 2 years. Participants were genotyped for GST polymorphisms (GSTT1, GSTM1 & GSTP1). Asthma was assessed and spirometry (GLI reference equations) was measured at 18 years. Regression models tested associations/confounders and interactions were assessed using likelihood ratio tests. Results: After adjustment for frequency of early life respiratory infection, doubling of days of paracetamol use was associated with a reduction in pre- and post-bronchodilator FEV1 (-1.47%, 95%CI -2.85, -0.10 of predicted; -1.41, 95%CI -2.70, -0.12 respectively) at 18 years. In those with GSTM1 null genotype, each doubling of days of use of paracetamol for non-respiratory reasons was associated with a reduction in FEV1 of 1.81% (95%CI -3.08, -0.54) at 18 years. This was not seen in those with GSTM1 present. No associations or interactions were found for asthma. Conclusions: We found evidence of association between early life paracetamol use and decreased lung function in adolescence, especially in individuals with GSTM1 null genotypes. Further investigation is needed to confirm this important findings.